IL-33/ST2 Pathway and Classical Cytokines in End-Stage Heart Failure Patients Submitted to Left Ventricular Assist Device Support: A Paradoxic Role for Inflammatory Mediators?

Background. Inflammation is a critical process contributing to heart failure (HF).We hypothesized that IL-33/ST2 pathway, a new mechanism regulated during cardiac stress, may be involved in the functional worsening of end-stage HF patients, candidates for left ventricular assist device (LVAD) implantation, and potentially responsible for their outcome. Methods. IL-33, ST2, and conventional cytokines (IL-6, IL-8, and TNF-α) were determined in cardiac biopsies and plasma of 22 patients submitted to LVAD implantation (pre-LVAD) and compared with (1) control stable chronic HF patients on medical therapy at the moment of heart transplantation without prior circulatory support (HT); (2) patients supported by LVAD at the moment of LVAD weaning (post- LVAD). Results. Cardiac expression of ST2/IL-33 and cytokines was lower in the pre-LVADthan in theHT group. LVADdetermined an increase of inflammatory mediators comparable to levels of the HT group. Only ST2 correlated with outcome indices after LVAD implantation. Conclusions. IL-33/ST2 and traditional cytokines were involved in decline of cardiac function of ESHF patients as well as in hemodynamic recovery induced by LVAD. IL-33/ST2 pathway was also associated to severity of clinical course.Thus, a better understanding of inflammation is the key to achieving more favorable outcome by new specific therapies. [ABSTRACT FROM AUTHOR]